The present invention relates to microfluidic devices and particularly to integration of modular microfluidic systems, and microfluidic devices for introducing fluid into another microfluidic device and for removing fluid from a microfluidic device.
There has been a growing interest in the manufacture and use of microfluidic systems for chemical and biochemical manufacturing processes and the acquisition of chemical and biological information. In particular, microfluidic systems allow complicated biochemical reactions to be carried out using very small volumes of liquid. These miniaturized systems increase the response time of the reactions, minimize sample volume, and lower reagent cost.
Traditionally, these microfluidic systems have been constructed in a planar fashion using photolithography to define channels on silicon or glass substrates and etching techniques to remove material from the substrate to form the channels. More recently, a number of methods have been developed that allow microfluidic devices to be constructed from plastic, silicone or other polymeric materials. Finally, novel microfluidic devices are described in co-pending U.S. patent application Ser. Nos. 09/453,026 and 09/453,029. These devices comprise one more stencils containing microstructures, which are disposed and sealed between substrate layers.
Thus, several different types of microfluidic devices, manufactured using several different techniques exist. For example, a preparation system could be constructed using silicon fabrication technology while a sorting device might be constructed using a silicone replication technique (see, Fu et al., Nature Biotechnology (199) 17: 1109-1111). In this situation, it would be impossible to develop a single integrated device.
Therefore, a great need exists for a device or method for connecting together different types of microfluidic devices that may have been manufactured using different techniques.
Moreover, discrete microfluidic components are often constructed that only perform partial functions of a complete system and there is a need to integrate such devices. For example, a silicon based microfluidic sample preparation system can be constructed. A separate microfluidic detection system could also be constructed. To make a completed device, the developer must typically go back to the development stage and develop processing techniques and steps that allow a single-integrated device to be developed.
Another issue in the development of microfluidic systems is the manner in which fluids and samples are injected into the device and removed from the device, which can often be a limiting problem with these devices.
The present invention provides a coupling device capable of connecting more than one microfluidic module together to form a larger, integrated system. It also provides a modular system of microfluidics components that can be combined in various configurations to construct completed microfluidic multichip modules (MMCMs) or modular microfluidic systems. In this manner, prototyping and manufacturing can be accomplished in a very rapid manner, since a complete set of building blocks can be constructed in bulk.
Further, the present invention provides a robust microfluidic coupling device for inputting fluids into a microfluidic device and removing fluids from those devices. These devices can be incorporated into existing industrial equipment.
Additionally, the present invention provides a microfluidic coupling device where the fluids within a microfluidic device can be transported off the device and easily manipulated. Microfluidic couplers of the present invention also allow a small amount of fluid to be removed from a microfluidic device with minimal loss of sample during the process.
Moreover, the invention provides a microfluidic coupling device that can accommodate the use of a vast array of liquid reagents or solutions. Different types of solvents and samples can be used, including but not limited to water based systems, organic based systems, biological materials solvated or dispersed within solvent, chemical systems, and others known by those skilled in the art. The microfluidic coupling devices of the present invention are constructed using a combination of traditional manufacturing techniques and novel chemistries and alignment procedures.
The present invention also incorporates electrodes into microfluidic coupling devices to perform electrokinetic flow, electrophoresis, and/or electronic detection within the devices.
Definitions
The term xe2x80x9cchannelxe2x80x9d or xe2x80x9cchamberxe2x80x9d as used herein is to be interpreted in a broad sense. Thus, it is not intended to be restricted to elongated configurations where the transverse or longitudinal dimension greatly exceeds the diameter or cross-sectional dimension. Rather, such terms are meant to comprise cavities or tunnels of any desired shape or configuration through which liquids may be directed. Such a fluid cavity may, for example, comprise a flow-through cell where fluid is to be continually passed or, alternatively, a chamber for holding a specified, discrete amount of fluid for a specified amount of time. xe2x80x9cChannelsxe2x80x9d and xe2x80x9cchambersxe2x80x9d may be filled or may contain internal structures comprising valves or equivalent components.
The term xe2x80x9cmicrofluidicxe2x80x9d as used herein is to be understood, without any restriction thereto, to refer to structures or devices through which fluid(s) are capable of being passed or directed, wherein one or more of the dimensions is less than 500 microns.
xe2x80x9cSubstantially planarxe2x80x9d as used herein refers to a structure having a height of between about 1 and 500 microns and a length and width each at least 100 times larger than the height.
A xe2x80x9cstencil layerxe2x80x9d as used herein refers to a discrete layer of material through which a channel or aperture has been cut, such that in the final device, the top and bottom surfaces of the microfluidic channel within the stencil layer are, formed from the bottom and top, respectively, of adjacent stencil or substrate layers. The stencils are preferably sandwiched between substrates, wherein the substrates are preferably substantially planar. Stencil layers are bonded by any technique that results in substantially liquid-tight channels within the device.